Platelet-rich plasma as a clinical treatment for bone, muscle, tendon, and cartilage injury has gained significant popularity in the field of orthopedic sports medicine in recent years due to its integral role in accelerating the cellular response to injury in the tissue repair and regeneration processes. The healing potential of platelet-rich plasma preparations is largely attributed to its dense concentration of growth factors and cytokines derived from platelets.
Platelet-rich plasma may be defined as an autologous concentrate of platelets in a small volume of plasma. Currently, platelet-rich plasma is defined only by the absolute quantity of platelets in the preparation, and not by the presence of other components. Normal platelet counts in blood range from approximately 150,000 to 350,000/μL, whereas platelet-rich plasma is often defined as at least 1,000,000 platelets/μL suspended in plasma. To ensure that platelets are suspended and do not form a clot, platelet-rich plasma is derived from anti-coagulated blood.
Multiple studies have demonstrated the role of platelet-rich plasma in accelerating and facilitating improved response to injury. The theoretical basis for the use of platelet-rich plasma in tissue repair is that large numbers of platelets appear immediately at the site of tissue injury and release growth factors and cytokines, thereby initiating the wound healing process. Thus, the enhancement of healing by the placement of a supraphysiologic concentration of platelets at the site of tissue injury is supported by basic science.
Many of the cytokines and growth factors believed to be responsible for the effects of platelet-rich plasma are contained within the α-granules of platelets, including, but not limited to, platelet-derived growth factor (PDGF), transforming growth factor β (TGF-β), insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2), fibroblast growth factor (FGF), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), Interleukin 8 (IL-8), keratinocyte growth factor (KGF), connective tissue growth factor (CTGF), platelet-derived angiogenesis factor (PDAF), platelet-derived endothelial growth factor (PDEGF), epithelial cell growth factor (ECGF), osteocalcin, osteonectin, fibrinogen, vitronectin, fibronectin, and thrombospondin. Platelet activation triggers degranulation and release of these factors, which, in turn, stimulates wound healing by promoting such actions as: (i) inducement of proliferation and differentiation of various cell types (e.g., stem cell, osteoblast, epidermal cell); (ii) enhancement/modulation of production of collagens and proteoglycans; and (iii) stimulation of angiogenesis.
Currently, treatment with platelet-rich plasma involves autologous use (e.g., the platelet-rich plasma is used to treat the individual from whom the blood was collected). Typically, a small amount of blood (usually 25-50 mL) is collected from the patient. Using centrifugation, the plasma, platelets and red blood cell components are separated and 3-5 mL of a platelet-rich fraction is extracted. This platelet-rich fraction may then be pre-activated with the clotting factor, thrombin, or directly injected back into the patient at the site of injury.
The present invention seeks to disclose human umbilical cord blood as an allogeneic source (e.g., from an individual other than the one receiving treatment) of platelet-rich plasma. Human umbilical cord blood is the blood that remains in the placenta and the attached umbilical cord after childbirth. The cord blood is composed of all of the elements found in whole blood, including red blood cells, white blood cells, plasma and platelets. Additionally, human umbilical cord blood is also rich in stem cells (e.g., hematopoietic stem cells, mesenchymal stem cells, multipotent adult progenitor cells, unrestricted somatic stem cells, endothelial progenitor cells). Thus, human umbilical cord blood is a viable alternative source for platelet-rich plasma preparations.